Brustovetsky Laboratory

The Brustovetsky laboratory studies the mechanisms of mitochondrial dysfunction, calcium deregulation, and neuronal loss in neurodegeneration such as Huntington’s disease. The Brustovetsky laboratory uses transgenic and knock-in mouse models of Huntington’s disease, cyclophilin D-knockout mice (Ppif -/-) and “mitochondrial calcium uniporter” (MCU)-knockout mice to study the mechanisms of Huntington’s disease (HD) and the role of calcium deregulation and mitochondrial injury in HD progression.

The overall goal of the Brustovetsky laboratory is to determine the mechanisms of calcium deregulation, mitochondrial dysfunction, and neuronal death in aging and age-related neurodegenerations such as Huntington’s disease.

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The Brustovetsky Lab utilizes highly purified isolated brain (synaptic and non-synaptic) mitochondria to analyze the effect of HD neuropathology on mitochondrial functions. To study isolated mitochondria, this lab team uses a computerized setup for simultaneous measurements of respiration, membrane potential, swelling, and calcium uptake by mitochondria. Using isolated mitochondria, the Brustovetsky laboratory studies the mechanisms of mitochondrial injury in HD and aging, particularly, the role of the mitochondrial permeability transition pore (PTP). The Brustovetsky laboratory also investigates the effect of HD pathology on reactive oxygen species (ROS) production in mitochondria.

In addition to isolated mitochondria, the Brustovetsky laboratory uses cultured neurons derived from newborn mice and rats as well as from human inducible pluripotent stem cells from healthy individuals and HD patients. The Brustovetsky laboratory uses cellular respirometry (Seahorse flux analyzer XF24), live-cell fluorescence wide-field and a laser spinning-disk confocal microscopy to investigate mitochondrial dysfunction, calcium deregulation, and ROS production in cultured neurons. In addition, the Brustovetsky laboratory uses electron microscopy to analyze mitochondrial morphological changes and western blotting and immunocytochemistry to evaluate expression of different proteins and investigate the release of mitochondrial proteins involved in programmed cell death, apoptosis.

Current Research Funding

NIH R01 NS098772

Recent Publications

2017

Hamilton, J., Brustovetsky, T., and Brustovetsky, N. (2017) Oxidative metabolism and Ca²⁺ handling in striatal mitochondria from YAC128 mice, a model of Huntington’s disease. Neurochemistry International, PMID: 28062223
2016

Lakhter, A., Hamilton, J., Konger, R., Brustovetsky, N., Broxmeyer, H., and Naidu, S. R. (2016) Glucose-independent acetate metabolism promotes melanoma cell survival and tumor growth. J. Biol. Chem. 291, 21869-21879. PMID: 27539851

Hamilton, J., Pellman, J. J., Brustovetsky, T., Harris, R. A., and Brustovetsky, N. (2016) Oxidative metabolism and Ca²⁺ handling in isolated brain mitochondria and striatal neurons from R6/2 Mice, a model of Huntington’s disease. Hum. Mol. Gen. 25, 2762-2775. PMID: 27131346

Patel, R. R., Barbosa, C., Brustovetsky, T., Brustovetsky, N., and Cummins, T. R. (2016) Aberrant epilepsy-associated mutant voltage-gated sodium channel activity can be targeted with cannabidiol. Brain 139, 2164-2181. PMID: 27267376
2015

Mantel, C.R., O’Leary, H. A., Chitteti, B.R., Huang, X., Cooper, S., Hangoc, G., Brustovetsky, N., Srour, E.F., Lee, M.R., Messina-Graham, S., Haas, D.M., Falah, N., Kapur, R., Pelus, L.M., Bardeesy, N., Fitamant, J., Ivan, M., Kim, K.-S., and Hal E. Broxmeyer, H.E. (2015) Enhancing hematopoietic stem cell transplantation efficacy by mitigating oxygen shock. Cell 161, 1553-1565. PMID: 26073944

Hamilton, J., Pellman, J.J., Brustovetsky, T., Harris, R., and Brustovetsky, N. (2015) Oxidative metabolism in YAC128 mouse model of Huntington’s disease. Hum. Mol. Gen. 24, 4862-4878. PMID: 26041817

Pellman, J.J., Hamilton, J., Brustovetsky, T., and Brustovetsky, N. (2015) Ca²⁺ handling in isolated brain mitochondria and cultured neurons derived from the YAC128 mouse model of Huntington’s disease. J. Neurochem. 134, 652-667. PMID: 25963273

Brustovetsky, N. (2015) Mutant huntingtin and elusive defects in oxidative metabolism and mitochondrial calcium Handling. Molecular Neurobiology 53, 2944-2953. PMID: 25941077
2014

Lakhter, A.J., Hamilton, J., Dagher, P.C., Mukkamala, S., Hato, T., Dong, X.C., Lindsey D Mayo, L.D., Harris, R.A., Shekhar, A., Ivan, M., Brustovetsky, N., and Naidu, S.R. (2014) Ferroxitosis: a cell death from modulation of oxidative phosphorylation and PKM2-dependent glycolysis in melanoma. Oncotarget 5, 12694-12703. PMID: 25587028

Brustovetsky, T., Pellman, J.J., Yang, X.-F., Khanna, R., and Brustovetsky, N. (2014) Collapsin response mediator protein 2 interacts with NMDA receptor and Na⁺/Ca²⁺ exchanger and regulates their functional activity. J. Biol. Chem. 289, 7470-7482. PMID: 24474686

Faculty Research Team

Nickolay Brustovetsky, PhD

Professor of Pharmacology & Toxicology

Read Bio Nickolay Brustovetsky, PhD

Additional Research Team Members

Other research team members in the Brustovetsky Lab include Tatiana Brustovetsky (research associate).